Atezolizumab and Bevacizumab With Photon Radiotherapy for Unresectable Hepatocellular Carcinoma

Sponsor
Chang Gung Memorial Hospital
Study ID
NCT06339424
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Atezolizumab — DRUG
    Atezolizumab 1200 mg will be administered as an IV infusion on Day 1 of each cycle, with cycles occurring every 3 weeks. The initial dose will be delivered over 60 (± 15) minutes, and if well-tolerated, subsequent infusions may be given over 30 minutes. For patients who achieve a complete response (CR) within one year of treatment, atezolizumab should be continuously used for a year. For patients who experience a partial response (PR), atezolizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive atezolizumab for 6 months. In the case of PD, atezolizumab should be discontinued at the time when PD is confirmed.
  • Bevacizumab — DRUG
    Bevacizumab 15 mg/kg will be administered as an IV infusion on Day 1 of each 3-week cycle. The initial dose will be delivered over 90 minutes (±15 minutes), and if well-tolerated, subsequent infusions may be given over 60 minutes. For patients who achieve a complete response (CR) within one year of treatment, bevacizumab should be continuously used for a year. In the case of patients experiencing a partial response (PR), bevacizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive bevacizumab for 6 months. In the event of PD, bevacizumab should be discontinued when PD is confirmed. Temporary withholding or dose reduction of bevacizumab is permitted if patients experience adverse events such as bleeding episodes, severe hypertension, or proteinuria at the discretion of the treating physician.
  • Photon radiotherapy — RADIATION
    * 39.6-72.6 Gy in 22 fractions for tumors ≤1 cm from the hepatic hilum, bowel, and heart. * 30-66 Gy in 10 fractions for tumors \>1 cm from the hepatic hilum, bowel, and heart. * 27.5-50 Gy in 5 fractions using stereotactic body radiation therapy (SBRT) techniques

Study Details

Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an improved objective response rate (ORR) of 27%, the majority of patients face HCC progression and liver failure \[Finn et al., N Engl J Med 2020\]. Developing a new combined treatment strategy to overcome resistance to anti-PD-L1 and anti-VEGF is essential to improve patient outcomes. Radiation treatment (RT) is highly efficacious in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Importantly, a recent retrospective cohort described that RT combined with atezolizumab plus bevacizumab was associated with favorable median overall survival of 16.1 months (Manzar et al, Cancers 2022). Our preclinical study (Hsieh et al., Science Immunology 2022) revealed that RT combined with PD-L1/PD-1 blockade induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, thereby potentiating the systemic antitumor T cell responses in murine tumor models. However, whether the combinatorial therapy with RT, atezolizumab, and bevacizumab can trigger synergistic antitumor effects and systemic immune mobilization has not yet been validated in clinical trials for unresectable HCC. Both atezolizumab/bevacizumab and X-ray RT are approved treatment methods for unresectable HCC by the U.S. and Taiwan Food and Drug Administration (FDA). The present phase II non-randomized trial aims to prospectively document the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with atezolizumab/bevacizumab combined with conventional photon radiotherapy.

Key Dates

Start date
Mar 30, 2024
Status verified
Apr 2025
Primary completion
Mar 30, 2029
Completion
Mar 30, 2031

Study Design

Enrollment
45 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Atezolizumab and bevacizumab with photon radiotherapy
    Patients undergo Atezolizumab and Bevacizumab with photon radiotherapy.

Primary Outcome Measure

Progression free survival (PFS) [ Time Frame: 12 months ]

Central Contacts

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